Alcoholism can alter structure, biochemistry, cellular and subcellular function of skeletal muscles and motor nerves; yet, the physiologic effects on neuromuscular function, as reflected by skeletal muscle force production, are virtually unexamined. We propose to study the contractile properties and susceptibility to fatigue of limb and respiratory muscles in alcoholic rates. We will examine the site of damage, the extent of muscular involvement, the possibility that inactivity compounds alcoholic effects, and an exercise strategy for counteracting neuromusuclar losses. We will test five major hypotheses: (1) We hypothesize that alcoholism reduces force production by skeletal muscle and that the mechanism is not myofibrillar damage. We will test this by measuring isometric contractile properties of the gastrocnemius in situ using indirect (neural) stimulation. Myofibrillar compromise will be tested using direct (surface electrode) stimulation. (2) We hypothesize that alcoholism increases susceptibility to fatigue. We will test this by measuring the rate of decline of tetanic force during repetitive stimulation of alcoholic and control gastrocnemius. (3) We hypothesize that alcoholic compromise is not limited to the limbs; that respiratory muscles also are weakened and fatigue more easily. To test this, we will compare isometric measurements from gastrocnemius in situ with measurements made on diaphragm in situ. Respiratory muscle damage would predispose alcoholic patients to ventilatory failure. (4) We hypothesize that alcoholism reduces physical activity and that chronic inactivity contributes to neuromuscular losses. We will measure spontaneous running of alcoholic and control rats with free access to exercise wheels. Comparing contractile measurements on these animals with similar data from sedentary and trained animals will help determine whether inactivity compounds alcoholic damage. (5) We hypothesize that endurance training can counteract strength and endurance losses that alcoholism induces. After long-term endurance training of alcoholic and control rats, we will again measure the contractile properties and susceptibility to fatigue of gastrocnemius.